title: [Effect of SNS-032 on biological activity of hematopoietic stem cells in mice].
abstract: This study was aimed to investigate the effect of SNS-032 (C17 H24 N4O2S2) on cell cycle, apoptosis, differentiation and self-renewal of hematopoietic stem cells (HSC) in mice. The self-renewal capability of bone marrow cells was measured by cobblestone forming cell test. The expressions of self-renewal regulation genes, cell cycle-related genes, apoptosis-related genes were measured by real-time PCR. The cell cycle status and apoptosis of HSC and HPC were detected by flow cytometry. The results showed that there was no significant difference of the frequency of HSC between SNS-032 and control group. The expressions of CDK1, CDK2, CDK7 and p27 decreased in HSC (P < 0.05) while the expressions of CDK4, CDK6, p21, p18, p19, Bcl-2, Bax, Puma, p53, Bim1, Sall4 and Notch1 showed no difference between SNS-032 group and control group (P > 0.05). The fraction of viable HSC in each phase of cell cycle remained unchanged after the treatment of SNS-032 (P > 0.05). Furthermore, there was no statistical difference in the apoptotic fractions between control and drug-treated groups (P > 0.05). It is concluded that SNS-032 induce apoptosis of cancer cells. Interestingly, SNS-032 has no significant inhibitory effect on self-renewal and differentiation of normal HSC, as well as no obvious effect inducing apoptosis of normal HSC and HPC.
authors.affiliation: Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Rui-Zhe
authors.initials: RZ
authors.lastname: Qi
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yuan
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Ying-Dai
authors.initials: YD
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010080:Oxazoles / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C484864:N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide; D010080:Oxazoles; D013844:Thiazoles